alexa MicroRNA and its Potential Use for the Treatment of Hepatitis C Virus Infection | OMICS International
ISSN: 1948-593X
Journal of Bioanalysis & Biomedicine

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

MicroRNA and its Potential Use for the Treatment of Hepatitis C Virus Infection

Wendi Zhao1, Xiaoqiong Duan2, Yujia Li2, Shilin Li2, Bing Liu2 and Limin Chen2,3*

1West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 China

2Institute of Blood Transfusion (IBT), Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, Sichuan 610052 China

3Toronto General Research Institute, University of Toronto, Toronto, ON M5G 1L6, Canada

*Corresponding Author:
Limin Chen
Toronto General Research Institute
University of Toronto
Toronto, ON M5G 1L6, Canada
Tel: 86-28-66430656
E-mail: [email protected], [email protected]

Received Date: February 28, 2014; Accepted Date: March 04, 2014; Published Date: March 08, 2014

Citation: Zhao W, Duan X, Li Y, Li S, Liu B, et al. (2014) MicroRNA and its Potential Use for the Treatment of Hepatitis C Virus Infection. J Bioanal Biomed 6: e125. doi: 10.4172/1948-593x.1000e125

Copyright: © 2014 Zhao W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Bioanalysis & Biomedicine

Hepatitis C Virus and Treatment Regimen

Hepatitis C virus (HCV) is a world-wide health problem with about 150 million people (3% of the world population) ( chronically infected. HCV is a single, positive-strand RNA virus that belongs to Flaviviridae family [1]. The full length of HCV genome contains 9.6 kb and encodes a polyprotein precursor of about 3000 amino acids that is then cleaved by host and viral proteases into three structural proteins (core, E1, and E2) and seven nonstructural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) [2,3].

Chronic HCV infection frequently results in progressive inflammation, fibrosis, cirrhosis, and an increased risk of hepatocellular carcinoma [4]. There are 6 major genotypes of HCV and genotype 1 is the most prevalent in many countries and also is the hardest to treat [5-9]. Standard treatment for HCV infection involves a combination therapy with pegylated interferon alpha (IFN) and ribavirin (RBV). However, only 40–50% patients infected with HCV genotype 1 and 80% in patients infected with HCV genotypes 2 or 3 achieve a sustained virologic response (SVR) [10,11]. Most recently, a direct acting antiviral agent (DAA)-based “triple therapy”, combining a HCV NS3/4A protease inhibitor with IFN/RBV, has been proposed to be the standard-of-care for genotype 1 infection and this triple therapy improved the SVR up to 75% [9,12]. Two NS3/4A protease inhibitors, Telaprevir and Boceprevir, have been approved by the Food and Drug Administration (FDA) [13] Although the adoption of triple therapy has improved response rates, the high cost, drug-drug interactions and severe side effects limit its use, especially in many developing countries where the treatment need most [13,14]. Therefore, it is necessary to explore other treatment options.

MicroRNAs and their Mimics or Anti-microRNAs

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression after transcription [15-18]. Mature miRNAs are transcribed from introns and exons of protein-coding genes or intergenic regions [19]. Transcription of miRNA genes forms primary transcripts (pri-miRNAs) that usually contain a hairpin structure consisting of a double-stranded stem and a terminal loop [20]. The stem-loop structure is then cleaved by an RNaseIII-like enzyme called drosha, together with its binding partner DGCR8 (DiGeorge syndrome critical region 8), to produce a ~70 nt precursor miRNA (pre-miRNA) [14,21-23]. The pre-miRNA is then transferred from the nucleus to the cytoplasm with the help of exportin-5 and its co-factor Ran-GTP (GTP bound form of cofactor Ras-related nuclear protein), where it is processed into a duplex structure by RNA polymerase III dicer [24]. Subsequently, one strand named “guide strand” binds to an Argonaute protein and is integrated into an RISC (RNA-induced silencing complex) that recognizes and binds to the target mRNA; the other strand is degraded and nonfunctional [15,25]. The binding of miRNA and its target results in degradation of the target mRNA or suppression of mRNA translation [26,27].

More than 1500 miRNAs (, released January 2012) have been identified in human genome and they are involved in almost every cell process, including development, differentiation, proliferation, death, disease pathology, and antiviral defence [28-31]. As a major host factor, miRNA represents an interesting field for studying the host-HCV interaction, ranging from HCV infection to the new targets for antiviral therapy [32]. In recent years, some oligonucleotide compounds were designed to mimic or sequester miRNAs as potential drug candidates and achieved promising results. For the miRNA mimic, the “guide strand” is identical to the interested miRNA and the “nonfunction strand” is modified and typically linked to a molecule such as cholesterol for enhanced cellular uptake [33]. Anti-miRs are modified antisense oligonucleotides harboring the full or partial complementary reverse sequence of a mature miRNA that can reduce the endogenous levels of an miRNA [33]. Two approaches to produce anti-miRs have been reported: one is 2-O-methyl-group (OMe)-modified oligonucleotides and the other is locked nucleic acid (LNA)-modified oligonucleotides [34,35].

In this review, we will focus on miRNAs that have been shown to have promising therapeutic effect for the treatment of HCV infection.

Treatment of HCV by T targeting miR-122

Of all the human miRNAs, miR-122 is one of the most studied. As a liver-specific and the most abundant miRNA (~70% of the liver total miRNAs), miR-122 plays a pivotal role in regulating hepatic functions [36]. Previous studies demonstrated that miR–122 is essential for HCV replication, which makes it an attractive host target for anti–HCV therapy [37]. miR-122 protects HCV from host immune attack by binding to two adjacent target sites in 5` untranslated region (5`UTR) of HCV RNA [38,39]. Miravirsen (SPC3649, Santaris Pharma, Hørsholm, Denmark), an anti-miR-122 agent complementary to miR-122, has been shown to have significant anti-HCV activity both in animal model and Phase I and IIa studies [40-42]. Treatment of HCV chronically infected chimpanzees with a LNA-modified oligonucleotide (SPC3649) achieved a prolonged and marked suppression of HCV viremia with no evidence for viral resistance or side effects in the treated animals [41]. Most recently, a randomized, doubleblind, placebo-controlled, ascending multiple dose-ranging Phase IIa study was finished in patients with chronic HCV genotype 1 infection [42]. The results showed that four-week injection of miravirsen provided significantly dose-dependent anti-HCV activity with a mean reduction of 2 to 3 logs from baseline in HCV RNA and 5 patients even had an undetectable HCV RNA levels after the treatment period [42]. However, considering miR-122 is an important host cellular factor involving in hepatocytes metabolism, although current data from the clinical study was promising, further investigation with long period of treatment and large sample size are needed to further clarify these concerns [32,43].

Other miRNAs that have Potential Use for the Treatment of HCV Infection

Besides miR-122, many other miRNAs were identified to be involved in HCV replication and infection. Similar to miR-122, miR-196 and miR-199a were reported to have direct interaction with HCV RNA by binding to NS5A-coding region and 5’UTR IRES respectively, which make them the most promising therapeutic targets [44,45]. miR-130a was reported to regulate HCV replication in vitro [46,47]. Chowdhury et al. identified IFITM1, which can inhibit HCV replication, as a potential miR-130a target [46]. From this study, it is reasonable to conclude that miR-130a is a positive regulator for HCV replication. However, most recently, Li et al found that the replication of HCV RNA was significantly decreased after overexpression of miR- 130a both in HCV replicon cells and J6/JFH HCV culture system [47]. These seemingly contradictory findings implied the complicated interaction between miR-130a and HCV and miR-130a as the potential target for HCV treatment. Although all these miRNAs are promising targets for HCV treatments, further studies are needed to uncover their cellular targets and their mechanism of action.

Future Directions

The advent of anti-miR-122 drugs is opening an exciting new era for hepatitis C treatment although more comprehensive and long-time effects should be pursued. Many other miRNAs have been reported to regulate HCV replication and they have great potential as therapeutic targets for HCV infection.


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 12358
  • [From(publication date):
    April-2014 - Sep 23, 2018]
  • Breakdown by view type
  • HTML page views : 8482
  • PDF downloads : 3876

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

bornova escort

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals


[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version